Abiraterone + Prednisone/Olaparib for Prostate Cancer

Not currently recruiting at 18 trial locations

Overseen By Study Coordinator

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Northwestern University

Must be taking: LHRH analogues

Must not be taking: CYP3A4 inhibitors, Antiretrovirals

Disqualifiers: Active malignancy, Seizures, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for men with advanced prostate cancer that no longer responds to hormone therapy. The focus is on medications like abiraterone (Zytiga), prednisone, and olaparib (Lynparza) to assess their effectiveness alone or together. Participants must have specific genetic changes in their cancer, such as ATM or BRCA mutations, which affect DNA repair. This trial targets those whose cancer has spread despite previous treatments and who can take oral medications. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications before joining the trial. Specifically, you must stop antiandrogen therapy at least 4 weeks before registration and certain other medications like ritonavir and St John's Wort at specified times before registration. However, you can continue taking a daily multivitamin, calcium, and Vitamin D.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that combining abiraterone with prednisone was generally safe for patients with prostate cancer. Serious side effects occurred less frequently in patients taking abiraterone compared to those on standard treatment—64.1% versus 71.8%. Common issues included fatigue and high blood pressure.

Research has shown that olaparib, when used alone, is also well-tolerated. Most patients did not experience worsening pain within six months of treatment. Some common side effects included nausea and anemia.

Studies indicate that the combination of abiraterone, prednisone, and olaparib is effective and safe. This combination can help delay cancer progression. However, patients might experience more side effects like fatigue and anemia. It is important to consult with a doctor to determine the best course of action. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine existing therapies in a novel way. Abiraterone and prednisone are well-known for reducing hormone levels that fuel prostate cancer, while olaparib is a PARP inhibitor that targets cancer cells' ability to repair DNA. The combination of abiraterone with olaparib is unique as it leverages both hormone suppression and DNA repair inhibition, potentially enhancing effectiveness against the cancer. This dual-action approach might offer benefits over standard treatments, such as androgen deprivation therapy alone, by attacking the cancer through different pathways simultaneously.

What evidence suggests that this trial's treatments could be effective for metastatic castration resistant prostate cancer?

This trial will evaluate different treatment combinations for advanced prostate cancer. Participants may receive Abiraterone with Prednisone, which research has shown to be effective for treating advanced prostate cancer that no longer responds to hormone therapy. In one study, patients taking this combination lived without their cancer worsening for an average of 33 months, compared to 14.8 months for those taking a placebo. Another group will receive Olaparib, which research indicates significantly helps patients with specific genetic mutations, such as BRCA1, BRCA2, and ATM, live longer. Patients on Olaparib had an average survival of 19.1 months, compared to 14.7 months with other treatments. Additionally, some participants will receive a combination of Olaparib with Abiraterone and Prednisone, which has been shown to reduce the risk of cancer progression by 34% compared to using Abiraterone alone, effectively delaying the progression of advanced prostate cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Maha Hussain, MD, FACP, FASCO

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

Men with metastatic castration-resistant prostate cancer and specific DNA repair defects (like ATM, BRCA mutations) can join. They must have a life expectancy of at least 6 months, be able to take oral meds, agree to use contraception for 3+ months after the trial, and not have had certain treatments like CYP17 inhibitors or chemotherapy for resistant disease. No major surgery or uncontrolled medical issues within 14 days before joining.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

I agree to a biopsy to check for DNA repair defects in my cancer.

I agree to use contraception during and for 3 months after the study.

Exclusion Criteria

I am allergic to medications similar to olaparib or abiraterone.

I have stopped taking all strong medications that affect liver enzymes.

Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or of long QT syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abiraterone, Olaparib, or Abiraterone + Olaparib in 28-day cycles

Up to 2 years

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Olaparib
• Prednisone

Trial Overview The study is testing three approaches: Abiraterone/Prednisone alone, Olaparib alone, or both combined in men with advanced prostate cancer who have genetic changes affecting DNA repair. It's an open-label phase II trial where patients are randomly assigned to one of the treatment arms.

How Is the Trial Designed?

Group I: Arm I: Abiraterone + Prednisone Active Control 2 Interventions

Abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily, days 1-28 in 28 day cycles.

Group II: Arm II: Olaparib Active Control 1 Intervention

Olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.

Group III: Arm III: Abiraterone + Prednisone + Olaparib Active Control 3 Interventions

Abiraterone 1000 mg orally once daily, prednisone 5 mg orally twice daily, olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.

Group IV: Olaparib Active Control 1 Intervention

Olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.

Abiraterone Acetate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33826036/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.5_suppl.367

Real-world discontinuation and efficacy data of abiraterone ... Background: Data from STAMPEDE trial confirmed Overall survival benefit for patients with high-risk localized or locally advanced prostate ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704174

Abiraterone plus Prednisone in Metastatic, Castration- ... The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group ( ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2059702922000527

Real-world experience of abiraterone acetate plus ... In 481 chemotherapy-naive mCRPC patients (median follow-up: 25 months), abiraterone plus prednisone was effective and safe.

5. zytigahcp.com zytigahcp.com/efficacy-and-safety/

Metastatic High-Risk CSPC LATITUDE Study A major efficacy outcome was overall survival. The pre-specified interim analysis after 406 deaths showed a statistically significant improvement in OS in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8105236/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00485303?term=AREA%5BInterventionSearch%5D(YONSA)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=6

An Efficacy and Safety Study of Abiraterone Acetate and ... The purpose of this study is to evaluate the efficacy and safety of abiraterone acetate in participants with advanced prostate cancer (a disease in which ...

8. mdpi.com mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ... More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent ...